PubMed Health⌕ Search

Biomedical subjects

H E Morgan

Publications and source records attributed to H E Morgan.

At least 19 recordsLinked to original sources
PubMed1995

American Heart Association-Bugher Foundation Centers for Molecular Biology in the Cardiovascular System.

BACKGROUND: The American Heart Association (AHA) and the Henrietta B. and Frederick H. Bugher Foundation in 1985 entered into a partnership to establish a group of Centers for Molecular Biology in the Cardiovascular System. The goal was to recruit and train young scientists with medical training to apply molecular and cellular biology knowledge and techniques to cardiovascular problems. METHODS AND RESULTS: Six Centers have been awarded (three in 1986 and three in 1991), and a total of 110 trainees have been involved as of June 30, 1994. Of these trainees, 77 were recruited and trained by the 1986 Centers. As of June 1994, 88% of these trainees remained in academic medicine and 54% progressed to higher academic ranks; 79% published papers in science and 66% in molecular biology; and 36% obtained extramural funding for their work. On this basis, the 1986 trainees appear to be well on their way to becoming successful academic cardiologists. CONCLUSIONS: The AHA-Bugher Foundation Center program has produced a cadre of cardiovascular scientists who are applying molecular biology knowledge to both basic and clinical problems.

Awards and Prizes↗
PubMed1995

Mechanisms of rapid growth in the neonatal pig heart.

During the first 2 weeks of life the left ventricular free wall of the neonatal pig heart grows rapidly. The mass of the left ventricular free wall (LVFW) increased from 2.22 +/- 0.10 g to 9.62 +/- 1.01 g while the right ventricular free wall (RVFW) increased from 2.03 +/- 0.24 g to 3.56 +/- 0.41 g from birth to 14 days of age. During the same period, the cellular volume of myocytes from the LVFW increased from 1075 microns3 to 3688 microns3 while myocytes from the RVFW increased in volume from 1511 microns3 to 2454 microns3. The number of RVFW myocytes did not change during the first 2 weeks of life, while the number of LVFW myocytes increased 28%. Myocytes from both ventricles were approximately 90% mononuclear from birth to 4-5 days of age. By 14 days, 67% of LVFW myocytes and 53% of RVFW myocytes were multinucleated. When growth of the heart was restrained by treatment of the piglet with enalapril maleate, the LVFW mass was reduced by 24% over 2 weeks compared to hearts from untreated piglets and was accounted for by a reduction in myocyte volume. Enalapril treatment did not alter the number of myocytes in either the LVFW or RVFW as compared to hearts from untreated piglets. After 14 days of enalapril treatment, the percentage of multinucleated cells was reduced in the LVFW and unchanged in the RVFW as compared to hearts from untreated piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Control of growth in neonatal pig hearts.

The pig heart grows at a maximal rate in the first 2-3 days of life due to a volume overload imposed on the heart at birth. Rates of ribosome formation and protein synthesis cannot be further accelerated during in vitro perfusion with agents that increase cyclic AMP, that bind to alpha 1-adrenergic receptors or that bind to angiotensin II receptors. Growth of the heart in vivo can be restrained by treatment with an angiotensin-converting enzyme inhibitor, enalapril maleate, or an angiotensin receptor antagonist, DuP 753. In the enalapril-treated heart, norepinephrine plus propranolol, but not angiotensin II, accelerated ribosome formation. Rapid growth of the left ventricle of pig heart during the first 10 days of life is due largely to eccentric hypertrophy.

Animals↗
PubMed1993

Alpha-adrenergic receptor agonists stimulate ribosome formation in hearts from enalapril-treated piglets.

Hearts from untreated or enalapril-treated piglets were used to measure rates of ribosome formation and total protein synthesis during perfusion as modified Langendorff preparations. Pretreatment of newborn piglets with enalapril maleate (5 mg, once daily for 3 days) resulted in a decreased rate of growth of the left ventricle. Addition of 1 microM angiotensin II to the perfusate had no effect on in vitro ribosome formation or protein synthesis in either the right or left ventricle of hearts from untreated or enalapril-treated piglets. Angiotensin II receptor number or affinity in the left ventricle was not decreased by enalapril treatment. In contrast, addition of combinations of 1 microM norepinephrine and 1 microM propranolol or 1 microM phenylephrine and 1 microM propranolol to the perfusate restored the rate of ribosome formation in the left ventricle of hearts from enalapril-treated piglets to that observed in the left ventricle of hearts from untreated piglets. Prazosin (100 nM) blocked the stimulatory effect of either norepinephrine or phenylephrine on ribosome formation in the left ventricle. Binding of [3H] prazosin to membranes from the left ventricle was unaltered by pretreatment of the piglet with enalapril maleate. Pretreatment of piglets with prazosin (1 mg, twice daily for 3 days) resulted in a small but significant decrease in mean arterial pressure as well as the rate of left ventricular growth. Pretreatment of piglets with hydralazine (10 mg, twice daily for 3 days) significantly reduced mean arterial pressure but did not alter left ventricular growth. These results support a role for alpha 1-adrenergic receptor stimulation in the regulation of neonatal cardiac growth.

Adrenergic alpha-Agonists↗
PubMed1993

Cuff sizes.

Explore the source record for details and available documents.

Blood Pressure Determination↗
PubMed1993

Cellular aspects of cardiac failure.

Intracellular signaling systems that are involved in growth of cardiac myocytes and that are modified in congestive heart failure include the alpha 1- and beta-adrenergic systems and angiotensin II. These systems include G-protein-linked hormone receptors and their membrane enzyme including adenylyl cyclase and phospholipase C. In addition, membrane enzymes, and adenylyl cyclase in particular, respond directly to stretch of the cell membrane with an increase in cAMP formation. Furthermore, interactions between stretch and hormonal stimuli can potentiate each other and result in enhanced signal generation.

Animals↗
PubMed1992

Acceleration of growth of cultured cardiomyocytes and translocation of protein kinase C.

Phorbol 12-myristate 13-acetate (PMA), norepinephrine (NE), and contraction stimulate cardiomyocyte growth (increased protein content). Differences exist in the time course and extent of protein and RNA accumulation. Cells plated at 4 x 10(6) cells/60-mm dish and arrested with 50 mM KCl demonstrated no significant growth. Treatment with PMA stimulated growth to a maximum of 17% at 48 h. In contrast, maximal stimulation of growth was 36% at 48 h and 31% at 72 h for contracting and NE-treated cells, respectively. Maximal stimulation of the capacity for protein synthesis (RNA content) was 32% for PMA-treated cells at 24 h compared with 59% and 77% for NE-treated and contracting cells, respectively, at 72 h. In support of a primary role for altered capacity in the regulation of protein synthesis, there was a significant correlation (r = 0.84) between RNA and protein contents that was independent of the stimulus used. Angiotensin II increased RNA content by 28% at 48 h but had no effect on growth up to 72 h. Growth stimulation and increased nuclear protein kinase C (PKC) activity were induced by contraction, NE, and PMA treatment and were inhibited by staurosporine (a PKC inhibitor), suggestive of a central role for PKC.

Alkaloids↗
PubMed1991

Phorbol ester stimulation of protein kinase C activity and ribosomal DNA transcription. Role in hypertrophic growth of cultured cardiomyocytes.

The mechanism by which phorbol esters induce hypertrophic growth of cardiomyocytes was investigated. Control and 4 alpha-phorbol 12,13-didecanoate-treated myocytes demonstrated a slow rate of growth as measured by the protein/DNA ratio and cell area. In contrast, treatment with phorbol 12-myristate 13-acetate (PMA) stimulated protein accumulation by 34%, while cell area was increased by 68% over control myocytes after 72 h. RNA content in PMA-treated myocytes was 33% higher than in control cells and 4 alpha-phorbol 12,13-didecanoate-treated cells after 72 h. Membrane-associated protein kinase C activity was transiently increased after PMA treatment but returned to normal by 48 h. Cytosolic protein kinase C activity was not significantly altered by PMA. Membrane-associated and cytosolic protein kinase C activities were not altered by 4 alpha-phorbol 12,13-didecanoate. Protein kinase C activity, RNA polymerase I activity, and the transcriptional rate of ribosomal DNA (rDNA) were increased in nuclei isolated from PMA-treated cells. However, consistent with a high rate of processing of pre-ribosomal RNA (pre-rRNA), the pool size of pre-rRNA relative to the 28 S rRNA was unaltered by PMA treatment. These data demonstrated that PMA-induced hypertrophic growth of cardiomyocytes was due to an increase in the capacity for protein synthesis (rRNA), and suggest that this results from protein kinase C mediated increase in the rate of transcription of rDNA.

Animals↗
PubMed1991

Angiotensin II and left ventricular growth in newborn pig heart.

The left ventricle of the neonatal pig heart is a model of rapid physiological cardiac growth that is dependent upon accelerated ribosome formation and increased RNA content. The goals of the present study were to investigate the role of angiotensin II in this rapid growth. Hearts from 3 d old control piglets or piglets that were treated with enalapril maleate, an angiotensin converting enzyme inhibitor, or DuP 753, an angiotensin II receptor antagonist, were used for measurements of left ventricular mass, RNA, DNA and protein. Hearts from enalapril-treated pigs also were used for measurements of rates of ribosome formation and total protein synthesis during perfusion as modified Langendorff preparations. Treatment of piglets with enalapril maleate resulted in decreased left ventricle/body wt ratio, RNA content, total RNA and total protein in the left ventricle. These parameters were unaffected in the right ventricle. In vitro perfusion of hearts from enalapril-treated piglets revealed decreased ribosome formation and total protein synthesis in the left ventricle. Piglets treated with DuP 753 had decreased left ventricle/body wt ratio as well as decreased RNA content, total RNA and RNA/DNA ratio in the left ventricle. These results suggest that angiotensin II may be required for rapid growth of neonatal pig hearts.

Angiotensin II↗
PubMed1991

Heat shock proteins in cultured human keratinocytes and fibroblasts.

Heat shock induces in cells the synthesis of specific proteins called heat-shock proteins. We have compared the induction of these proteins in human keratinocytes, skin fibroblasts, and a human epithelial tumor cell line following exposure to weak and strong inducing agents (heat, cadmium sulphate, and sodium arsenite). The induction of heat shock proteins was measured in cells by one-dimensional gel electrophoresis of [35S] methionine-labeled proteins and by immunofluorescence using a specific HSP72 monoclonal antibody. Both HSP90 and HSP116 were constitutively expressed in these cell types. Exposure of these cells to weak inducing agents such as heat or cadmium sulphate resulted in the synthesis of HSP72 and HSP90, whereas HSP28 and HSP116 synthesis was detected in keratinocytes and fibroblasts following exposure to the strong inducing agent sodium arsenite. In addition, sodium arsenite induced the synthesis of HSP46 in human keratinocytes. Immunofluorescence demonstrated a rapid and reversible accumulation of the 72-kD heat shock protein within the nucleolus of heat-stressed human keratinocytes and fibroblasts.

Arsenic↗
PubMed1991

Control of growth in the neonatal pig heart.

The newborn heart is an excellent model in which to study cardiac growth because the neonatal period is a normal situation in which the left ventricle (LV) grows rapidly and the right ventricle grows slowly. Accelerated LV growth is in response to mechanical, neural, and endocrine changes at birth. Faster growth of the LV is accounted for by greater capacity for protein synthesis, as evidenced by greater RNA content. At 18 h of life, ribosomes are formed in preference to total heart protein, but at 48 h of life, faster rates of both ribosome formation and total protein synthesis are observed. In the LV of hearts from 2-day-old pigs, these rates are insensitive to the addition of glucagon, 1-methyl-3-isobutylxanthine, or a combination of norepinephrine and propranolol. These observations could result because of maximal growth stimulation already present in the LV of the newborn heart. To restrain LV growth in the neonatal period, we treated pigs with enalapril maleate, an angiotensin II-converting enzyme inhibitor. Enalapril blocked growth of the LV as well as the increase in RNA content. When hearts from enalapril-treated pigs were perfused in vitro, rates of protein synthesis and ribosome formation in the LV were lower. These studies suggest that angiotensin II is an important factor accounting for rapid growth of the neonatal heart in response to pressure overload at birth.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Accelerated ribosome formation and growth in neonatal pig hearts.

Rapid growth (5 mg dry heart/h) of the left ventricular free wall (LVFW) in the newborn pig heart accompanied by lack of growth of the right ventricular free wall (RVFW) represents a unique natural model of cardiac enlargement that is free of pathophysiological influences. By 3 days of life, LVFW was 71% larger than at 4 h of age. Rates of protein synthesis were measured during perfusion of isolated pig hearts with bicarbonate buffer containing glucose, lactate, insulin, and plasma concentrations of amino acids of an aortic pressure of 60 mmHg. In hearts from pigs that were 18 h of age, rates of protein synthesis were the same in RVFW and LVFW, but in 2-day-old pigs the rate was 52% greater in LVFW than RVFW. During the first 3 days of life, RNA content (mg/g) increased 3.4-fold faster in LVFW than RVFW. When RNA content was expressed per total heart portion, the increase was 7.9-fold greater. Because approximately 85% of total RNA is rRNA, these values indicated much more rapid formation of ribosomes in the LVFW than RVFW. When ribosome formation was measured in vitro in hearts from 48-h-old pigs, rates of formation were 39% greater in LVFW than RVFW, and at 18 h of age, ribosome formation was 40% faster in LVFW than RVFW. These findings indicated that formation of new ribosome preceded accelerated synthesis of total heart proteins. These findings indicated that rapid growth of LVFW compared with no growth of RVFW was associated with a 67% faster rate of ribosome formation and a 32% greater rate of protein synthesis.

Aging↗
PubMed1990

Signal transduction in myocardial hypertrophy.

Transduction of stretch of the ventricular wall into accelerated growth and ultimately hypertrophy of cardiac muscle cells is a cyclic AMP (cAMP) dependent phenomenon. When stretch was induced in isolated perfused rat hearts by an increase in aortic pressure from 60 to 120 mmHg, protein synthesis was accelerated during the second hour of perfusion. Only a brief exposure to higher aortic pressure (2 min) was required to elicit this effect. Elevation of aortic pressure also increased cAMP content. Other interventions that increased cAMP content such as glucagon increased second hour rates of protein synthesis. Stretch of the ventricular wall had a more rapid effect on ribosome formation. During the first hour of perfusion, increased aortic pressure raised rates of 60S ribosomal subunit formation by 38% in the absence of added insulin and 35% in the presence of the hormone. Ribosome formation was also accelerated by addition of glucagon. The muscarinic cholinergic agonist, methacholine blocked the effects of elevated aortic pressure on protein synthesis, ribosome formation, and cAMP content. These studies indicate that stretch of the ventricular wall is transduced into greater cAMP content and that this intracellular messenger is one of the substances responsible for accelerated ribosome formation and protein synthesis.

Animals↗
PubMed1990

Catecholamines, glucagon, energy metabolism and protein degradation in rat heart.

Isoproterenol, epinephrine, phenylephrine and glucagon inhibited proteolysis in isolated perfused rat hearts. All of these agents had a positive inotropic effect, while isoproterenol and glucagon were shown to increase cyclic AMP content. The catecholamines, but not glucagon, partially depleted the adenine nucleotide pool, but the creatine-phosphate/creatine ratio was unchanged or increased. Isoproterenol markedly increased lactate production and caused release of lactate dehydrogenase. The effects of isoproterenol on these parameters, including proteolysis, were blocked by propranolol and verapamil. Isoproterenol also inhibited proteolysis when perfusate calcium was reduced from 2.5 to 0.5 mM; but, in this circumstance, isoproterenol did not deplete ATP. In hearts arrested with tetrodotoxin, neither isoproterenol nor glucagon inhibited proteolysis and neither of them depleted ATP. Both hormones still increased cyclic AMP content. These findings suggest that cyclic AMP may not be involved in the control of proteolysis, and that the effects of isoproterenol and glucagon are mediated via effects on contractility. The studies stress the importance of preventing adenine nucleotide depletion and controlling contractility in experiments on the mechanisms of inotropic agents on cardiac protein turnover.

Adenine Nucleotides↗
PubMed1989

Accelerated rates of ribosomal RNA synthesis during growth of contracting heart cells in culture.

Contractile activity of neonatal cardiac myocytes stimulated hypertrophic growth as compared with nonbeating cells that were depolarized with 50 mM KCl. Growth of contracting myocytes was associated with an increased rRNA content as measured by the total RNA/DNA ratio. The fractional rates of rRNA synthesis (K8) and rRNA degradation were determined in contracting and nonbeating myocytes to assess their relative contributions in increasing rRNA content during growth. The values for K8 were calculated from the specific radioactivity of 3'-[3H]UMP in 18 and 28 S rRNA after purification by hybridization to cloned rDNA. The cellular [3H]UTP pool served as the precursor for rRNA synthesis in myocytes that were labeled with 50 microM [3H]uridine. K8 values for 18 and 28 S rRNA in contracting myocytes were accelerated by 59 and 53%, respectively, after 3 days as compared with nonbeating myocytes. Calculations of the rate of cellular rRNA synthesis, which took into account the increased content of myocyte rRNA, revealed that synthesis of both 18 and 28 S rRNA was accelerated 2-fold after 2 days of contraction. The derived values for degradation of 18 and 28 S rRNA were increased marginally in contracting myocytes, but cellular rRNA degradation rates averaged 57% higher. The difference between cellular rates of rRNA synthesis and degradation in contracting myocytes accounted for the 30% increase in rRNA content. These data demonstrated that increased rRNA content in contracting myocytes resulted from acceleration of the fractional rate of rRNA synthesis.

Animals↗
PubMed1989

Elevated aortic pressure, calcium uptake, and protein synthesis in rat heart.

Elevation of aortic pressure from 60 to 120 mmHg increased the initial rate of 45Ca2+ uptake and the steady-state level that was achieved. The increase in uptake was as great after the first 10 min of pressure elevation as it was after aortic pressure had been at 120 mmHg for 1 h. When aortic pressure was returned to 60 mmHg for 30 min after 1 h at 120 mmHg, calcium uptake was restored to the control value. Elevation of perfusate Ca2+, from 0.5 mM to 2.9 and 5.0 mM increased oxygen consumption and decreased creatine phosphate/creatine ratios in hearts supplied glucose but had not effect on the rate of total protein synthesis. When hearts were supplied pyruvate to maintain high energy phosphates, an increase in perfusate Ca2+ from 0.5 to 2.9 mM did not accelerate total protein synthesis or ribosome formation. These studies provide no support for a role for extracellular Ca2+ availability in mediating the effects of elevated aortic pressure on total protein synthesis and ribosome formation.

Animals↗